EA016360B1 - Ингибиторы 11-бета-гидроксистероид дегидрогеназы 1, фармацевтическая композиция на их основе и их применение - Google Patents
Ингибиторы 11-бета-гидроксистероид дегидрогеназы 1, фармацевтическая композиция на их основе и их применение Download PDFInfo
- Publication number
- EA016360B1 EA016360B1 EA200870476A EA200870476A EA016360B1 EA 016360 B1 EA016360 B1 EA 016360B1 EA 200870476 A EA200870476 A EA 200870476A EA 200870476 A EA200870476 A EA 200870476A EA 016360 B1 EA016360 B1 EA 016360B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- compounds
- pharmaceutically acceptable
- mmol
- acceptable salt
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
- 239000003112 inhibitor Substances 0.000 title description 7
- 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title 1
- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 26
- 230000000694 effects Effects 0.000 abstract description 12
- 239000005557 antagonist Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 31
- -1 derivatives of adamantyl acetamides Chemical class 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 20
- 208000035475 disorder Diseases 0.000 description 19
- 206010012601 diabetes mellitus Diseases 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 208000001145 Metabolic Syndrome Diseases 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 14
- 229960000890 hydrocortisone Drugs 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 11
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 10
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 10
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 229960004544 cortisone Drugs 0.000 description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 241000282412 Homo Species 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- 206010020772 Hypertension Diseases 0.000 description 7
- 208000008589 Obesity Diseases 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 108010004469 allophycocyanin Proteins 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 235000020824 obesity Nutrition 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000004949 mass spectrometry Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 5
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 5
- 206010022489 Insulin Resistance Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229910052693 Europium Inorganic materials 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- BQENDLAVTKRQMS-SBBGFIFASA-L Carbenoxolone sodium Chemical compound [Na+].[Na+].C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C([O-])=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](OC(=O)CCC([O-])=O)C1(C)C BQENDLAVTKRQMS-SBBGFIFASA-L 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 3
- 229960000530 carbenoxolone Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 239000012285 osmium tetroxide Substances 0.000 description 3
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229940037128 systemic glucocorticoids Drugs 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- ZVYAFVOHYMRKHP-UHFFFAOYSA-N tert-butyl-(3,5-dichlorophenoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC(Cl)=CC(Cl)=C1 ZVYAFVOHYMRKHP-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- GZPKMEKJXBJIEZ-UHFFFAOYSA-N (2,6-dichloro-4-methoxyphenyl)methanol Chemical compound COC1=CC(Cl)=C(CO)C(Cl)=C1 GZPKMEKJXBJIEZ-UHFFFAOYSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- WWFRBIPLCLSKNH-UHFFFAOYSA-N 2,6-dichloro-4-hydroxybenzaldehyde Chemical compound OC1=CC(Cl)=C(C=O)C(Cl)=C1 WWFRBIPLCLSKNH-UHFFFAOYSA-N 0.000 description 2
- KBAGYDQLZMGHMT-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dichloro-5-methoxybenzene Chemical compound COC1=CC(Cl)=C(CBr)C(Cl)=C1 KBAGYDQLZMGHMT-UHFFFAOYSA-N 0.000 description 2
- GUXFHOKKFSZLTH-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dichloro-5-phenylmethoxybenzene Chemical compound ClC1=C(CBr)C(Cl)=CC(OCC=2C=CC=CC=2)=C1 GUXFHOKKFSZLTH-UHFFFAOYSA-N 0.000 description 2
- 208000004611 Abdominal Obesity Diseases 0.000 description 2
- 208000011732 Abnormal glucose homeostasis Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 241000402754 Erythranthe moschata Species 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 102100030817 Liver carboxylesterase 1 Human genes 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000282849 Ruminantia Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000012911 assay medium Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
- 201000008980 hyperinsulinism Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- JDKQTIKEGOOXTJ-UHFFFAOYSA-N pent-4-enoyl chloride Chemical compound ClC(=O)CCC=C JDKQTIKEGOOXTJ-UHFFFAOYSA-N 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 235000013594 poultry meat Nutrition 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- OVPWEQROJNJHAG-UHFFFAOYSA-N (1-naphthalen-1-ylnaphthalen-2-yl)-diphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1)C1=CC=CC=C1 OVPWEQROJNJHAG-UHFFFAOYSA-N 0.000 description 1
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- WTHWVGFNEDOQGB-UHFFFAOYSA-N (2,6-dichloro-4-phenylmethoxyphenyl)methanol Chemical compound C1=C(Cl)C(CO)=C(Cl)C=C1OCC1=CC=CC=C1 WTHWVGFNEDOQGB-UHFFFAOYSA-N 0.000 description 1
- PQCXFUXRTRESBD-UHFFFAOYSA-N (4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C=C1 PQCXFUXRTRESBD-UHFFFAOYSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- VOYUCTPCAWSYTF-UHFFFAOYSA-N 2,6-dichloro-4-methoxybenzaldehyde Chemical compound COC1=CC(Cl)=C(C=O)C(Cl)=C1 VOYUCTPCAWSYTF-UHFFFAOYSA-N 0.000 description 1
- FLHXTURECXRMQK-UHFFFAOYSA-N 2,6-dichloro-4-phenylmethoxybenzaldehyde Chemical compound ClC1=C(C=O)C(Cl)=CC(OCC=2C=CC=CC=2)=C1 FLHXTURECXRMQK-UHFFFAOYSA-N 0.000 description 1
- UQZPGHOJMQTOHB-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-ethylethanamine Chemical compound ClCCN(CC)CCCl UQZPGHOJMQTOHB-UHFFFAOYSA-N 0.000 description 1
- VPOMSPZBQMDLTM-UHFFFAOYSA-N 3,5-dichlorophenol Chemical compound OC1=CC(Cl)=CC(Cl)=C1 VPOMSPZBQMDLTM-UHFFFAOYSA-N 0.000 description 1
- KMUKXPQVPQUCDB-UHFFFAOYSA-N 4-(trifluoromethyl)piperidine;hydrochloride Chemical compound Cl.FC(F)(F)C1CCNCC1 KMUKXPQVPQUCDB-UHFFFAOYSA-N 0.000 description 1
- OJOFMLDBXPDXLQ-UHFFFAOYSA-N 4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)NC1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100022734 Acyl carrier protein, mitochondrial Human genes 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 102000052567 Anaphase-Promoting Complex-Cyclosome Apc1 Subunit Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- UGSHHRVZMJMAEA-UHFFFAOYSA-N B1C(CCC2)CCCC12CC1=CC=CC=C1 Chemical compound B1C(CCC2)CCCC12CC1=CC=CC=C1 UGSHHRVZMJMAEA-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282817 Bovidae Species 0.000 description 1
- NRSKLCCINAQQQL-UHFFFAOYSA-N CCN(CC)S.F.F.F Chemical compound CCN(CC)S.F.F.F NRSKLCCINAQQQL-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010065941 Central obesity Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 101150040795 EIS1 gene Proteins 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 101000678845 Homo sapiens Acyl carrier protein, mitochondrial Proteins 0.000 description 1
- 101000938676 Homo sapiens Liver carboxylesterase 1 Proteins 0.000 description 1
- 101000611240 Homo sapiens Low molecular weight phosphotyrosine protein phosphatase Proteins 0.000 description 1
- 101000965660 Homo sapiens U6 snRNA-associated Sm-like protein LSm8 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010056997 Impaired fasting glucose Diseases 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100345589 Mus musculus Mical1 gene Proteins 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108091006463 SLC25A24 Proteins 0.000 description 1
- 101710169844 Sesquipedalian-1 Proteins 0.000 description 1
- 206010049416 Short-bowel syndrome Diseases 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102100040948 U6 snRNA-associated Sm-like protein LSm8 Human genes 0.000 description 1
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 244000309465 heifer Species 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 238000011141 high resolution liquid chromatography Methods 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 210000005119 human aortic smooth muscle cell Anatomy 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- IYLFKXATVSYTQV-UHFFFAOYSA-N tert-butyl-(chloromethoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCl IYLFKXATVSYTQV-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical group C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74556506P | 2006-04-25 | 2006-04-25 | |
| PCT/US2007/067353 WO2007127765A1 (en) | 2006-04-25 | 2007-04-25 | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200870476A1 EA200870476A1 (ru) | 2009-04-28 |
| EA016360B1 true EA016360B1 (ru) | 2012-04-30 |
Family
ID=38421497
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200870476A EA016360B1 (ru) | 2006-04-25 | 2007-04-25 | Ингибиторы 11-бета-гидроксистероид дегидрогеназы 1, фармацевтическая композиция на их основе и их применение |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8148534B2 (enExample) |
| EP (1) | EP2016071B1 (enExample) |
| JP (1) | JP5101602B2 (enExample) |
| CN (1) | CN101432277B (enExample) |
| AU (1) | AU2007244863B2 (enExample) |
| BR (1) | BRPI0710875A2 (enExample) |
| CA (1) | CA2649822C (enExample) |
| EA (1) | EA016360B1 (enExample) |
| ES (1) | ES2429570T3 (enExample) |
| MX (1) | MX2008013656A (enExample) |
| WO (1) | WO2007127765A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101541747B (zh) * | 2006-04-21 | 2012-11-14 | 伊莱利利公司 | 作为11-β-羟基甾族化合物脱氢酶1的抑制剂的联苯基酰胺内酰胺衍生物 |
| CA2647677C (en) * | 2006-04-21 | 2014-03-18 | Eli Lilly And Company | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| AU2007240450B2 (en) | 2006-04-21 | 2011-12-22 | Eli Lilly And Company | Cyclohexylimidazole lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| AU2007244955B2 (en) * | 2006-04-24 | 2011-12-08 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| AU2007244960B2 (en) | 2006-04-24 | 2012-03-01 | Eli Lilly And Company | Substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EA016415B1 (ru) | 2006-04-24 | 2012-04-30 | Эли Лилли Энд Компани | Ингибиторы 11-бета-гидроксистероид-дегидрогеназы типа 1 |
| BRPI0710050A2 (pt) | 2006-04-25 | 2011-08-02 | Lilly Co Eli | composto, composição farmacêutica, e, intermediário |
| ATE471311T1 (de) | 2006-04-25 | 2010-07-15 | Lilly Co Eli | Inhibitoren von11-beta- hydroxysteroiddehydrogenase 1 |
| BRPI0710469A2 (pt) | 2006-04-28 | 2011-08-16 | Lilly Co Eli | composto, composição farmacêutica, e, intermediário |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| EP2243479A3 (en) | 2009-04-20 | 2011-01-19 | Abbott Laboratories | Novel amide and amidine derivates and uses thereof |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8933024B2 (en) | 2010-06-18 | 2015-01-13 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8710050B2 (en) | 2011-03-08 | 2014-04-29 | Sanofi | Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| JP2022507585A (ja) * | 2018-11-16 | 2022-01-18 | ブリストル－マイヤーズ スクイブ カンパニー | １－（（３ｓ，４ｒ）－４－（２，６－ジフルオロ－４－メトキシフェニル）－２－オキソピロリジン－３－イル）－３－フェニル尿素の製造のための合成方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005108361A1 (en) * | 2004-05-07 | 2005-11-17 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| WO2006049952A1 (en) * | 2004-10-29 | 2006-05-11 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| CN101001836B (zh) | 2004-05-07 | 2010-12-22 | 詹森药业有限公司 | 作为11-β羟基类固醇脱氢酶抑制剂的吡咯烷-2-酮和哌啶-2-酮衍生物 |
| US8138342B2 (en) | 2004-10-12 | 2012-03-20 | High Point Pharmacueticals, LLC | 11β-hydroxysteroid dehydrogenase type 1 active spiro compounds |
| KR101368228B1 (ko) | 2004-11-10 | 2014-02-27 | 인사이트 코포레이션 | 락탐 화합물 및 약제로서의 이의 용도 |
| ATE399546T1 (de) * | 2004-12-20 | 2008-07-15 | Lilly Co Eli | Cycloalkyl-lactam-derivate als inhibitoren von 11-beta-hydroxysteroiddehydrogenase 1 |
| US7834194B2 (en) * | 2004-12-21 | 2010-11-16 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US20090264650A1 (en) | 2005-03-31 | 2009-10-22 | Nobuo Cho | Prophylactic/Therapeutic Agent for Diabetes |
| WO2007084314A2 (en) | 2006-01-12 | 2007-07-26 | Incyte Corporation | MODULATORS OF 11-ß HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| CN101541747B (zh) * | 2006-04-21 | 2012-11-14 | 伊莱利利公司 | 作为11-β-羟基甾族化合物脱氢酶1的抑制剂的联苯基酰胺内酰胺衍生物 |
| AU2007240450B2 (en) * | 2006-04-21 | 2011-12-22 | Eli Lilly And Company | Cyclohexylimidazole lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CA2647677C (en) * | 2006-04-21 | 2014-03-18 | Eli Lilly And Company | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| AU2007244960B2 (en) * | 2006-04-24 | 2012-03-01 | Eli Lilly And Company | Substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| AU2007244955B2 (en) | 2006-04-24 | 2011-12-08 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EA016415B1 (ru) * | 2006-04-24 | 2012-04-30 | Эли Лилли Энд Компани | Ингибиторы 11-бета-гидроксистероид-дегидрогеназы типа 1 |
| ATE471311T1 (de) * | 2006-04-25 | 2010-07-15 | Lilly Co Eli | Inhibitoren von11-beta- hydroxysteroiddehydrogenase 1 |
| BRPI0710050A2 (pt) | 2006-04-25 | 2011-08-02 | Lilly Co Eli | composto, composição farmacêutica, e, intermediário |
| BRPI0710469A2 (pt) * | 2006-04-28 | 2011-08-16 | Lilly Co Eli | composto, composição farmacêutica, e, intermediário |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
-
2007
- 2007-04-25 EP EP07761237.2A patent/EP2016071B1/en not_active Not-in-force
- 2007-04-25 US US12/297,910 patent/US8148534B2/en not_active Expired - Fee Related
- 2007-04-25 BR BRPI0710875-3A patent/BRPI0710875A2/pt not_active IP Right Cessation
- 2007-04-25 WO PCT/US2007/067353 patent/WO2007127765A1/en not_active Ceased
- 2007-04-25 ES ES07761237T patent/ES2429570T3/es active Active
- 2007-04-25 AU AU2007244863A patent/AU2007244863B2/en not_active Ceased
- 2007-04-25 CN CN200780014900XA patent/CN101432277B/zh not_active Expired - Fee Related
- 2007-04-25 CA CA2649822A patent/CA2649822C/en not_active Expired - Fee Related
- 2007-04-25 JP JP2009507937A patent/JP5101602B2/ja not_active Expired - Fee Related
- 2007-04-25 EA EA200870476A patent/EA016360B1/ru not_active IP Right Cessation
- 2007-04-25 MX MX2008013656A patent/MX2008013656A/es active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005108361A1 (en) * | 2004-05-07 | 2005-11-17 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| WO2006049952A1 (en) * | 2004-10-29 | 2006-05-11 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Non-Patent Citations (1)
| Title |
|---|
| DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; "Preparation of 3-benzylpyrrolidin-2-one and N-benzylimidazolidin-2-one derivatives as prophylactic/therapeutic agents for diabetes" XP002449024 abstract; compounds RN 911722-70-8 and RN 911724-34-0 & WO 2006/104280 A (TAKEDA PHARMACEUTICAL COMPANY [JP]; CHO NOBUO [JP]; KASAI SHIZUO [JP];) 5 October 2006 (2006-10-05) * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2016071B1 (en) | 2013-07-24 |
| CA2649822A1 (en) | 2007-11-08 |
| EA200870476A1 (ru) | 2009-04-28 |
| CN101432277A (zh) | 2009-05-13 |
| US20090275613A1 (en) | 2009-11-05 |
| ES2429570T3 (es) | 2013-11-15 |
| US8148534B2 (en) | 2012-04-03 |
| EP2016071A1 (en) | 2009-01-21 |
| WO2007127765A1 (en) | 2007-11-08 |
| MX2008013656A (es) | 2008-11-10 |
| AU2007244863A1 (en) | 2007-11-08 |
| BRPI0710875A2 (pt) | 2012-01-10 |
| JP2009535358A (ja) | 2009-10-01 |
| CN101432277B (zh) | 2013-12-25 |
| AU2007244863B2 (en) | 2012-01-19 |
| CA2649822C (en) | 2013-08-13 |
| JP5101602B2 (ja) | 2012-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA015516B1 (ru) | Ингибиторы 11-бета-гидроксистероид дегидрогеназы 1 | |
| EA014717B1 (ru) | ПРОИЗВОДНЫЕ ЛАКТАМА ЦИКЛОГЕКСИЛИМИДАЗОЛА В КАЧЕСТВЕ ИНГИБИТОРОВ 11-β-ГИДРОКСИСТЕРОИД ДЕГИДРОГЕНАЗЫ 1 | |
| JP5101602B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| JP5189078B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| JP5225980B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのピエリジニル置換ピロリジノン | |
| JP5324427B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| EA016415B1 (ru) | Ингибиторы 11-бета-гидроксистероид-дегидрогеназы типа 1 | |
| JP5269765B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| EA014718B1 (ru) | Производные бифениламидлактама в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 | |
| KR20160103986A (ko) | N-벤질 트립탄트린 유도체, 및 이의 제조 방법 및 적용 | |
| CN106967005B (zh) | 一种能抑制ido的化合物、其制备方法及其用途 | |
| CN111848573B (zh) | 苯并噻吩酰胺类化合物及其制备方法和用途 | |
| EP3619193B1 (en) | Amino-aryl-benzamide compounds and methods of use thereof | |
| US8269010B2 (en) | 3-amino-pyridine derivatives for the treatment of metabolic disorders | |
| WO2016159576A2 (ko) | 1,2 나프토퀴논 유도체 및 이의 제조방법 | |
| WO2003057213A2 (en) | Cyclohexano- and cycloheptapyrazole derivative compounds, for use in diseases associated with the 5-ht2c receptor | |
| MC1744A1 (fr) | Derives de phenylethanolamines | |
| CN117143039B (zh) | 一种苯并五元氮环类化合物、其制备方法及医药用途 | |
| CN111848572B (zh) | 酰胺类化合物及其制备方法和用途 | |
| US8314092B2 (en) | Substituted [(5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoic acid compounds as dual activity H1 inverse agonists/5-HT2A antagonists | |
| CN110903224A (zh) | 一种芳基磺酰胺类化合物、其制备方法、药物组合物及用途 | |
| JP2007522181A (ja) | シクロオキシゲナーゼ−１及びシクロオキシゲナーゼ−２阻害剤としての置換アゼチジン化合物、ならびにそれらの調製、および薬剤としての使用 | |
| CN109824655B (zh) | 穿心莲内酯化合物及其制备方法和用途 | |
| TW202430505A (zh) | 萘醯胺類化合物、其製備方法及其應用 | |
| CN121517394A (zh) | 一种取代的吡啶丙酸衍生物及其用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM |
|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): RU |